DNA Sequencing for Genetic Disorders

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Disqualifiers: Dementia, Intellectual disability, Hematological cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

110000 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial collects information on how sequencing a patient's deoxyribonucleic acid (DNA) (i.e., the genetic material) could impact their health care. This study also develops and improves ways to include genomic information from DNA sequencing into the electronic health record to create a more complete "Health Tapestry" for each participant. Sequencing of a patient's DNA leads to the detection of genetic variants some of which determine risk for disease development. Discovery of those genetic variants in a patient could result in prevention, earlier diagnosis or better therapy of disease.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It seems unlikely that you would need to stop, as the study focuses on DNA sequencing and not on medication effects.

What data supports the effectiveness of the treatment DNA Sequencing for Genetic Disorders?

DNA sequencing, especially next-generation sequencing, has shown promise in diagnosing rare genetic disorders and improving patient care by identifying disease-related genetic changes. It has been effective in diagnosing conditions that are difficult to identify through traditional methods and has potential applications in personalized medicine. ^{1 2 3 4 5}

Is DNA sequencing generally safe for humans?

DNA sequencing is generally safe, with significant problems occurring in only a small fraction of tests (0.33% to 0.38%), and moderate or high levels of harm in just 0.008% of cases. No lawsuits or disciplinary actions were reported in over 277,000 tests, indicating a low risk of harm. ^{3 6 7 8 9}

How does DNA sequencing differ from other treatments for genetic disorders?

DNA sequencing, particularly next-generation sequencing (NGS), is unique because it allows for a comprehensive analysis of multiple genes at once, which can identify rare mutations and novel genetic diagnoses that might not be considered with traditional single-gene tests. This approach is especially useful for diagnosing rare and genetically complex disorders quickly and cost-effectively. ^{4 10 11 12 13}

Research Team

Konstantinos N. Lazaridis, M.D.

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

This trial is for adults over 18 who can send a saliva sample from within the US, are Mayo Clinic patients with email and web access, and can consent to participate. Pregnant women may join but should consult their OB provider for prenatal genetic concerns. People with bone marrow transplants, active blood cancers, New York residency, or conditions affecting study participation (like dementia) cannot join.

Inclusion Criteria

Ability to collect and ship saliva sample within the United States

Able to provide informed written consent

I am pregnant or planning to become pregnant and understand this study doesn't replace prenatal tests.

Exclusion Criteria

Other co-morbidity which would in physician's opinion interferes with patient's ability to participate in the study (e.g., reduced ability to comprehend e.g., dementia, intellectual disability, fluency in consent language)

I had a bone marrow transplant from a donor.

I have or had blood cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Biospecimen Collection and Genetic Analysis

Participants receive a saliva kit, register with Helix, and undergo collection of saliva sample. Sequencing is completed by Helix, and genetic findings are shared with participants and their primary provider.

8-12 weeks

1 visit (virtual)

Genetic Counseling and Clinical Confirmation

Participants with positive results are offered genetic counseling and are encouraged to seek clinical confirmatory testing. Results are scanned into the electronic health record.

4-8 weeks

2 visits (in-person)

Follow-up

Participants are monitored for health-care utilization and acceptance of genomic testing. Medical records are reviewed, and participants are surveyed.

Up to 5 years

Treatment Details

Interventions

• DNA Sequencing

Trial Overview The trial is exploring how DNA sequencing affects healthcare by integrating genomic data into electronic health records to create a 'Health Tapestry.' It aims to identify genetic variants that could influence disease risk and improve prevention, diagnosis, or treatment.

Participant Groups

Group I: Screening (biospecimen collection, genetic analysis) Experimental Treatment 4 Interventions

Participants receive a saliva kit, register with Helix then undergo collection of saliva sample which is returned o Helix. Participants also receive an online link to complete the About Me family history. Once sequencing is completed by Helix, ancestry/trait information and genetic findings are shared with participants and their primary provider, if applicable. Participants with positive results are offered genetic counseling and are encouraged to seek clinical confirmatory testing. Following clinical confirmation, results are scanned into the electronic health record. Participants may also undergo the collection of blood, urine, and stool samples for future studies.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Human genomic sequencing can provide valuable insights for diagnosis, prognosis, and treatment across various medical fields, but its widespread use is limited by a lack of evidence showing improved patient outcomes in those without specific testing indications.

The paper reviews clinical outcome studies in genomic medicine, highlighting the challenges of generating robust evidence to support the integration of next-generation sequencing into standard patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building evidence and measuring clinical outcomes for genomic medicine. Peterson, JF., Roden, DM., Orlando, LA., et al.[2020]

Next-generation sequencing (NGS) technologies allow for a more comprehensive approach to genetic diagnosis, moving from a traditional gene-by-gene method to broader techniques like diagnostic gene panel sequencing (DPS), diagnostic exome sequencing (DES), and diagnostic genome sequencing (DGS).

These NGS methods can be cost-effective for diagnosing rare genetic disorders with high variability, and they have the potential to identify new disease-related genes that were not previously associated with human diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in the Clinical Application of Next-Generation Sequencing. Ki, CS.[2021]

Next-generation gene sequencing can sequence an individual's entire genome in under a week for $5000 to $10,000, making it a promising tool for diagnosing complex diseases that are hard to identify through traditional methods.

While there have been successful applications in diagnosing diseases and improving tumor management, significant challenges remain, including data interpretation, physician training, and the need for rigorous studies to validate its effectiveness in larger patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The promise and challenges of next-generation genome sequencing for clinical care. Johansen Taber, KA., Dickinson, BD., Wilson, M.[2022]

The National Institutes of Health Genetic Testing Registry (GTR) is a comprehensive online resource that provides detailed information about genetic tests available worldwide, including their purpose, methods, and validity.

The GTR allows for easy access to information about genetic testing, helping healthcare providers and patients make informed decisions about genetic disorders, as all data is voluntarily submitted and regularly updated by test providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The NIH genetic testing registry: a new, centralized database of genetic tests to enable access to comprehensive information and improve transparency. Rubinstein, WS., Maglott, DR., Lee, JM., et al.[2021]

Next-generation sequencing is revolutionizing genomic medicine by enabling faster, cheaper, and more precise genetic testing, which is particularly beneficial for diagnosing rare genetic conditions in symptomatic children.

The implementation of these advanced technologies raises important ethical issues related to test design, patient consent, and the communication of results, highlighting the need for real-world deployment to fully understand these challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomic medicine: evolving science, evolving ethics. Soden, SE., Farrow, EG., Saunders, CJ., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Building evidence and measuring clinical outcomes for genomic medicine. [2020]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Genetic health professionals' experiences with initiating reanalysis of genomic sequence data. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

[Genome sequencing and personalized medicine: perspectives and limitations]. [2015]

4. Korea (South) pubmed.ncbi.nlm.nih.gov

Recent Advances in the Clinical Application of Next-Generation Sequencing. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

The promise and challenges of next-generation genome sequencing for clinical care. [2022]

6. England pubmed.ncbi.nlm.nih.gov

The NIH genetic testing registry: a new, centralized database of genetic tests to enable access to comprehensive information and improve transparency. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Genomic medicine: evolving science, evolving ethics. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Frequency of problems during clinical molecular-genetic testing. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Fluorescent detection and isolation of DNA variants using stabilized RecA-coated oligonucleotides. [2010]

10. United States pubmed.ncbi.nlm.nih.gov

Candidate-gene criteria for clinical reporting: diagnostic exome sequencing identifies altered candidate genes among 8% of patients with undiagnosed diseases. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Advances in the Genetic Testing of Neuromuscular Diseases. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Axons to Exons: the Molecular Diagnosis of Rare Neurological Diseases by Next-Generation Sequencing. [2022]

13. China pubmed.ncbi.nlm.nih.gov

[Exome sequencing: an efficient strategy for identifying the causative genes of monogenic disorders]. [2011]